1. Technical Field
This document relates to methods and materials involved in modulating deubiquitinases and ubiquitinated polypeptides (e.g., tumor suppressors such as wild-type p53 polypeptides). For example, this document relates to methods and materials for increasing or decreasing deubiquitinase expression or activity, methods and materials for stabilizing or de-stabilizing ubiquitinated polypeptides, and methods and materials for treating cancer.
2. Background Information
p53 is a tumor suppressor that is mutated in more than 50% of human cancers and whose major function is regulating cell fate following cellular stress and repressing the propagation of damaged cells (Lane, 1992; Riley et al., 2008; Vogelstein et al., 2000). p53 functions as a transcription factor, and through its target genes regulates a variety of cellular functions, from cellular senescence, to energy metabolism, DNA repair, cell differentiation, cell cycle progression and apoptosis. In addition to the activation of transcription, p53 can also act as a repressor of transcription, as it does in the suppression of CD44, a protein implicated in tumorigenesis (Godar et al., 2008). Finally, p53 also has transcription-independent functions, such as regulating apoptosis through protein-protein interactions (Moll et al., 2005).